Producing uniform, very small particles is a common processing challenge for pharmaceutical substances. In general, smaller particles provide two very desirable qualities of pharmaceuticals, namely higher bioavailability and a higher dissolution rate. In U.S. Pat. No. 5,314,506 there is described a method using two impinging jets to achieve uniform particles. However, the particles formed using the process in U.S. Pat. No. 5,314,506 are only as small as 3 microns in size and the majority of the crystals formed are in the range of 3-20 microns.
The general process by which these prior art small particles are produced involves two impinging liquid jets positioned within a well stirred flask to achieve high intensity micromixing. At the point where the two jets strike one another a very high level of supersaturation exists. As a result of this high supersaturation, crystallization occurs extremely rapidly within the small mixing volume at the impingement point of the two liquids. Since new crystals are constantly nuceleating at the impingement point, a very large number of crystals are produced. As a result of the large number of crystals formed, the average size remains small, although not all the crystals formed are small in size.
The novel apparatus and process of this invention utilizes impinging jets to achieve high intensity micromixing in the crystallization process. The background of high intensity micromixing is discussed in detail in U.S. Pat. No. 5,314,506, which is incorporated by reference herein.